SpringerLink
Log in

Radioanalytical and nuclear techniques in trace metal toxicology research

  • Published:
Journal of Radioanalytical and Nuclear Chemistry Aims and scope Submit manuscript

Abstract

Trace metal toxicology research aimed at generating human-relevant information for risk assessment requires the use of sensitive and sophisticated analytical techniques to determine typically µg kg−1 or lower concentrations of trace metals in tissues, cells, intracellular components of laboratory animals and humans. The results of these techniques are needed for an understanding of the biochemical mechanisms and bio-transformations involving trace metals. In this context, radioanalytical and nuclear methods plays a pivotal role. In order to give an idea of typical results which can be obtained by radioanalytical and nuclear techniques when used in combination with biochemical and molecular biology techniques of cellular fractionation we report here some typical studies carried out by means of non-carrier added radiotracers with high specific activity, and neutron activation analysis (NAA). The investigations have been performed in the context of an integrated and complementary in vivo and in vitro approach that uses both animal and human test systems. Applications reported concern: (1) the in vivo work on laboratory animals (brain regional thallium distribution in rats and identification of thallium binders in testis, by means of 201+202Tl); (2) in vitro investigations on cells of animal origin (arsenic uptake and biomethylation in rat brain aggregates, neurons, microglia and astrocytes as well as speciation of vanadate in Balb/3T3 cells, by means of 73As and 48V, respectively); (3) in vitro experiments on cell of human origin (intracellular behavior of cadmium in human umbilical cord blood stem cells, by means of 109Cd); (4) analytical determinations of trace metals in tissues of general population and patients potentially affected by metal-related disease, by means of NAA. The analytical determinations carried out allowed to relate total element concentrations in cells to the results of investigations at the intracellular and molecular levels with the goal of identifying the biochemical components that interact with trace metals. These findings demonstrate the great potential of radioanalytical and nuclear techniques in the context of an integrated in vivo-in vitro strategy adopted in trace metal toxicology research for a mechanistically-based hazard characterization concerning the exposure to low doses of trace metals.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12

Similar content being viewed by others

References

  1. Tchounwou PB, Yedjou CG, Patlolla AK, Sutton DJ (2012) Heavy metals toxicity and the environment. EXS 101:133–164. https://doi.org/10.1007/978-3-7643-8340-4_6

    Article  PubMed  PubMed Central  Google Scholar 

  2. OJ: JOL_1980_229_R_0011_008 Council Directive 80/778/EEC of 15 July 1980 relating to the quality of water intended for human consumption. https://publications.europa.eu/en/publication-detail/-/publication/c0ad00db-b82c-46ab-af4b-4691225fbd6d/language-en

  3. OJ: L 327, 3 December 1980, Council Directive 80/1107/EEC of 27 November 1980 on the protection of workers from the risks related to exposure to chemical, physical and biological agents at work. 23:8–13. https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=OJ:L:1980:327:FULL&from=EN

  4. OJ: L 225, 13.8.1987, Council Directive 87/416/EEC of 21 July 1987 amending Directive 85/210/EEC on the approximation of the laws of the Member States concerning the lead content of petrol. 30:33–34. https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=OJ:L:1987:225:FULL&from=EN

  5. OJ: L 226, 3.8.1989, Council Directive 89/458/EEC of 18 July 1989 amending with regard to European emission standards for cars below 1,4 litres, Directive 70/220/EEC on the approximation of the laws of the Member States relating to measures to be taken against air pollution by emissions from motor vehicles. 32:1–3. https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=OJ:L:1989:226:FULL&from=EN

  6. OJ: L 242, 30.8.1991, Council Directive 91/441/EEC of 26 June 1991 amending Directive 70/220/EEC on the approximation of the laws of the Member States relating to measures to be taken against air pollution by emissions from motor vehicles. 34:1–106. https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=OJ:L:1991:242:FULL&from=EN

  7. Commission Regulation (EC) No 466/2001 of 8 March 2001 setting maximum levels for certain contaminants in foodstuffs. 1–25. https://publications.europa.eu/en/publication-detail/-/publication/52b2484d-39e0-4aa9-ba19-4b13a887bb1c/language-en8

  8. **e W, Peng C, Wang H, Chen W (2017) Health risk assessment of trace metals in various environmental media, crops and human hair from a mining affected area. Int J Environ Res Public Health 14:1595. https://doi.org/10.3390/ijerph14121595

    Article  CAS  PubMed Central  Google Scholar 

  9. Worth PA, Balls M (2002) Alternative (non-animal) methods for chemicals testing: current status and future prospects. Report Prepared by ECVAM and the ECVAM working group on chemicals ATLA30 Suppl1

  10. Schilter B, Holzhäuser D, Cavin C, Huggett AC (1996) An integrated in vivo and in vitro strategy to improve food safety evaluation. Trends Food Sci Technol 7:327–332

    Article  Google Scholar 

  11. Foa V, Ferioli A (1992) The microdose problem and the most commonly used metals. Sci Total Environ 120:117–125

    Article  CAS  PubMed  Google Scholar 

  12. Sabbioni E, Girardi F (1977) Metallobiochemistry of heavy metal pollution: nuclear and radiochemical techniques for long term-low level exposure (LLE) experiments. Sci Total Environ 7:145–179

    Article  CAS  PubMed  Google Scholar 

  13. Mounicou S, Szpunar J, Lobinski R (2009) Metallomics: the concept and methodology. Chem Soc Rev 38:1119–1138. https://doi.org/10.1039/b713633c

    Article  CAS  PubMed  Google Scholar 

  14. Goetz L, Sabbioni E, Marafante E (1980) Cyclotron production of 107.109Cd for use in metallobiochemistry of heavy metal pollution. Radiochem Radioanal Lett 45:51–60

    CAS  Google Scholar 

  15. Goetz L, Sabbioni E, Marafante E, Birattari C, Bonardi M (1981) Biochemical studies of current environmental levels of trace elements: cyclotron production of radiothallium and its use for metabolic investigations on laboratory animals. J Radioanal Chem 67:183

    Article  CAS  Google Scholar 

  16. Sabbioni E, Bonardi M, Tanet G, Da Kang L, Gallorini M, Weckermann B, Castiglioni M (1989) Metallobiochemistry of current environmental levels of trace metals: a new method of cyclotron production of 48V for toxicological studies. J Radioan Nucl Chem 134:199–208

    Article  CAS  Google Scholar 

  17. Sabbioni E, Fortaner S, Manenti S, Groppi F, Bonardi M, Bosisio S, Di Gioacchino M (2015) The metallobiochemistry of ultratrace levels of platinum group elements in the rat. Metallomics 7:267–276

    Article  CAS  PubMed  Google Scholar 

  18. Padovese P, Gallieni M, Brancaccio D, Pietra R, Fortaner S, Sabbioni E, Minoia C, Markakis K, Berlin A (1992) Trace elements in dialysis fluids and assessment of the exposure of patients on regular hemodialysis, hemofiltration and continuous ambulatory peritoneal dialysis. Nephron 61:442–448

    Article  CAS  PubMed  Google Scholar 

  19. Bonda PLF, Porrini R, Rizzio E, Pietra R, Fortaner S, Sabbioni E (2001) Trace metals in oral mucosa in relation to the lichen ruber planus pathology. A preliminary study carried out by neutron activation analysis. J Trace Elem Med Biol 15:79–83

    Article  CAS  PubMed  Google Scholar 

  20. Minoia C, Sabbioni E, Apostoli P, Pietra R, Pozzoli L, Gallorini M, Nicolaou G, Alessio L, Capodaglio E (1990) Trace element reference values in tissues from inhabitants of the European community I. A study of 46 elements in urine, blood and serum of Italian subjects. Sci Total Environ 95:89–105

    Article  CAS  PubMed  Google Scholar 

  21. Sabbioni E, Minoia C, Pietra R, Fortaner S, Gallorini M, Saltelli A (1992) Trace element reference values in tissues from inhabitants of the European Community. II. Examples of strategy adopted and trace element analysis of blood, lymph nodes and cerebrospinal fluid of Italian subjects. Sci Total Environ 120:39–61

    Article  CAS  PubMed  Google Scholar 

  22. Bosisio S, Fortaner S, Rizzio E, Groppi F, Salvini A, Bode P, Wolterbeek B, Di Gioacchino M, Sabbioni E (2015) Nuclear and spectrochemical techniques in developmental metal toxicology research. Whole-body elemental composition of Xenopus Laevis Larvae. J Radioanal Nucl Chem 303:2127–2134

    CAS  Google Scholar 

  23. Council Directive 86/609/EEC of 24 November 1986 on the approximation of laws, regulations and administrative provisions of the Member States regarding the protection of animals used for experimental and other scientific purposes

  24. Glowinski J, Iversen LL (1966) Regional studies of catecholamines in the rat brain. I. The disposition of [3H]norepinephrine, [3H]dopamine and [3H]dopa in various regions of the brain. J Neurochem 3:655–669

    Article  Google Scholar 

  25. Sabbioni E, Fortaner S, Bosisio S, Farina M, Del Torchio R, Edel J, Fischbach M (2010) Metabolic fate of ultratrace levels of GeCl4 in the rat and in vitro studies on its basal cytotoxicity and carcinogenic potential in Balb/3T3 and HaCaT cell lines. J Appl Toxic 30:34–41

    Article  CAS  Google Scholar 

  26. Honegger P, Monnet-Tschudi F (2001) Aggregating neural cell cultures. In: Fedoroff S, Richardson A (eds) Protocols for neural cell culture, vol 1, 3rd edn. Humana Press, Ottawa, pp 199–218

    Chapter  Google Scholar 

  27. Kinsner A, Pilotto V, Deininger S, Brown GC, Coecke S, Hartung T, Bal-Price A (2005) Inflamatory neurodegeneration induced by lipoteichoic acid from Staphylococcus aureus is mediated by glia activation, nitrosative and oxidative stress and caspase activation. J Neurochem 95:1132–1143

    Article  CAS  PubMed  Google Scholar 

  28. Kinsner A, Boveri M, Hareng L, Brown GC, Coecke S, Hartung T, Bal-Price A (2006) Highly purified lipoteichoic acid induced pro-inflammatory signaling in primary culture of rat microglia through Toll-like receptor 2: selective potentiation of nitric oxide production by muramyl dipeptide. J Neurochem 99:596–607

    Article  CAS  PubMed  Google Scholar 

  29. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275

    CAS  PubMed  Google Scholar 

  30. Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55–63

    Article  CAS  PubMed  Google Scholar 

  31. Tam KH, Charbonneau SM, Bryce F, Lacroix G (1978) Separation of arsenic metabolites in dog plasma and urine following intravenous injection of 74As. Anal Biochem 86:505–511

    Article  CAS  PubMed  Google Scholar 

  32. Mazzotti F, Sabbioni E, Ghiani M, Cocco B, Ceccatelli R, Fortaner S (2001) In vitro assessment of cytotoxicity and carcinogenic potential of chemicals: evaluation of cytotoxicity induced by 58 metal compounds in Balb/3T3 cell line. ATLA 29:601–611

    CAS  PubMed  Google Scholar 

  33. Sabbioni E, Pozzi G, Pintar A, Casella L, Garattini S (1991) Cellular retention, cytoxicity and morphological transformation by vanadium (IV) and vanadium (V) in BALB/3T3 cell lines. Carcinogenesis 12:47–52

    Article  CAS  PubMed  Google Scholar 

  34. Di Gioacchino M, Petrarca C, Perrone A, Farina M, Sabbioni E, Hartung T, Martino S, Esposito DL, Lotti LV, Mariani-Costantini R (2008) Autophagy as an ultrastructural marker of heavy metal toxicity in human cord blood hematopoietic stem cells. Sci Total Environ 392:50–58

    Article  PubMed  Google Scholar 

  35. Karbowska B (2016) Presence of thallium in the environment: sources of contaminations, distribution and monitoring methods. Environ Monit Assess 188:640. https://doi.org/10.1007/s10661-016-5647-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Sabbioni E, Goetz L, Birattari C, Bonardi M (1981) Environmental biochemistry of current environmental levels of heavy metals: preparation of radiotracers with very high specific radioactivity for metallobiochemical experiments on laboratory animals. Sci Total Environ 17:257–276

    Article  CAS  PubMed  Google Scholar 

  37. Formigli L, Scelsi R, Poggi P, Gregotti C, Di Nucci A, Sabbioni E, Gottardi L, Manzo L (1986) Thallium-induced testicular toxicity in the rat. Environ Res 40:531–539

    Article  CAS  PubMed  Google Scholar 

  38. Osorio-Rico L, Santamaria A, Galván-Arzate S (2017) Thallium toxicity: general issues, neurological symptoms, and neurotoxic mechanisms. Adv Neurobiol 18:345–353

    Article  PubMed  Google Scholar 

  39. Galván-Arzate S, Pedraza-Chaverrí J, Medina-Campos ON, Maldonado PD, Vázquez-Román B, Ríos C, Santamaría A (2005) Delayed effects of thallium in the rat brain: regional changes in lipid peroxidation and behavioral markers, but moderate alterations in antioxidants, after a single administration Food. Chem Toxicol 43:1037–1045

    Article  Google Scholar 

  40. Ríos C, Galván-Arzate S, Tapia R (1989) Brain regional thallium distribution in rats acutely intoxicated with Tl2SO4. Arch Toxicol 63:34–37

    Article  PubMed  Google Scholar 

  41. Rade JE, Marafante E, Sabbioni E, Gregotti C, Di Nucci A, Manzo L (1982) Placental transfer and retention of 201Tl-thallium in the rat. Toxicol Lett 11:275–280

    Article  CAS  PubMed  Google Scholar 

  42. Cullen WR (2014) Chemical mechanism of arsenic biomethylation. Chem Res Toxicol 27:457–461. https://doi.org/10.1021/tx400441h

    Article  CAS  PubMed  Google Scholar 

  43. Florea AM, Busselberg D (2013) The two opposite facets of arsenic: toxic and anticancer drug. J Local Global Health Sci 2013:1–11. https://doi.org/10.5339/jlghs.2013.1

    Article  Google Scholar 

  44. Zurich MG, Monnet-Tschudi F, Honegger P (1994) Long-term treatment of aggregating brain cell cultures with low concentrations of lead acetate. Neurotoxicol 15:715–720

    CAS  Google Scholar 

  45. Honegger P, Matthieu JM (1985) Aggregating brain cell cultures: a model to study meylination and demeylination. In: Jeserich G, Althaus HH, Waehneldt TV (eds) Cellular and molecular biology of meylination. Springer, Berlin, pp 155–170

    Google Scholar 

  46. Saffiotti U, Bertolero F (1989) Neoplastic transformation of BALB/3T3 cells by metals and the quest for induction of a metastatic phenotype. Biol Trace Elem Res 21(475–82):39

    Google Scholar 

  47. Sabbioni E, Pozzi G, Devos S, Pintar A, Casella L, Fishbach M (1993) The intensity of vanadium (V)-indiced cytotoxicity and morphological transformation in Balb/3T3 cells is dependent on glutathione-mediated bioreduction to V(IV). Carcinogenesis 14:2565–2568

    Article  CAS  PubMed  Google Scholar 

  48. Davila JC, Cezar GG, Thiede M, Strom S, Miki T, Trosko J (2004) Use and application of stem cells in toxicology. Toxicol Sci 79:214–223

    Article  CAS  PubMed  Google Scholar 

  49. Filella M, Belzile N, Yu-Wei Chen (2013) Human exposure to antimony. IV. Contents in human blood. Crit Rev Environ Sci Technol 43:2071–2105. https://doi.org/10.1080/10643389.2013.790741

    Article  Google Scholar 

  50. Krachler M, Wirnsberger GH (2000) Long-term changes of plasma trace element concentrations. Chronic Hemodial Patients Blood Purif 18:138–143

    Article  CAS  Google Scholar 

  51. Tonelli M, Wiebe N, Hemmelgarn B, Klarenbach S, Field C, Manns B, Thadhani R, Gill J for The Alberta Kidney Disease Network (2009) Trace elements in hemodialysis patients: a systematic review and meta-analysis. BMC Med 19(7):25. https://doi.org/10.1186/1741-7015-7-25

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Aging Research Centre (CeSI), G.d’Annunzio University Foundation, Via Colle dell’Ara, 66100, Chieti, Italy

    Enrico Sabbioni & Mario Di Gioacchino

  2. LASA, Università degli Studi di Milano and INFN−Milano, Via F.lli Cervi 201, 20090, Segrate, MI, Italy

    Enrico Sabbioni, Flavia Groppi & Simone Manenti

  3. Phi Science S.r.l, Via alla Rocca 3, 28041, Arona, NO, Italy

    Massimo Farina

Authors
  1. Enrico Sabbioni
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mario Di Gioacchino
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Massimo Farina
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Flavia Groppi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Simone Manenti
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Enrico Sabbioni.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sabbioni, E., Di Gioacchino, M., Farina, M. et al. Radioanalytical and nuclear techniques in trace metal toxicology research. J Radioanal Nucl Chem 318, 1749–1763 (2018). https://doi.org/10.1007/s10967-018-6321-3

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10967-018-6321-3

Keywords

Search

Navigation